Optimization of Extrusion Treatments, Quality Assessments, and Kinetics Degradation of Enzyme Activities during Storage of Rice Bran.

Over the years, extrusion has been a multi-step thermal technique that has proven to be the most effective process to stabilize rice bran (RB). This study aimed to investigate the effects of extrusion treatment and temperature (15, 25, and 40 °C) on the storage stability, lipid oxidation, peroxidase, and peroxide values, free fatty acids, fatty acid composition, and protein variations of RB over 60 days. The study offers novel insights into the changes in RB's protein and amino acid compositions during extrusion and storage, which has not been extensively explored in prior research. After extrusion processing, peroxidase activity (POD) and lipase activity (LPS) were significantly reduced. However, peroxide value (PV), free fatty acids (FFA), and malondialdehyde content (MDA) observed a significantly increased by 0.64 mEqO2/kg, 8.3 mg/100 g, and 0.0005 µmol/L respectively. The storage stability of RB after extrusion shows that the POD, LPS, FFA, PV, and MDA were positively correlated with storage duration and temperature. The oleic acid/linoleic acid ratio in processed RB by extrusion had no significant changes during storage. The total and essential/non-essential amino acid ratios showed a downward trend of 5.26% and 8.76%, respectively. The first-order kinetics was the best-fitting model to describe the enzymatic inactivation and degradation of extruded RB during storage. The extrusion treatment did not affect the crude protein and the essential subunits of protein. Overall, the optimized extrusion procedure exhibited promising results in stabilizing the RB.

The Effects of Thermal Treatment on Lipid Oxidation, Protein Changes, and Storage Stabilization of Rice Bran.

Rice bran is a nutrient-rich and resource-dense byproduct of rice milling. The primary cause of rice bran utilization limitation is oxidative deterioration and inadequate storage facilities. Improving stability to extend the shelf-life of rice bran has thus become an utmost necessity. This study aimed to stabilize raw fresh rice bran (RB) by using dry heat methods at 120 °C (233, 143, and 88 min) and 130 °C (86, 66, and 50 min). The results indicated that after dry heat pretreatment, peroxidase levels were at 90%, and the storage stability of dry-heat-stabilized RB was better. However, with an increase in treatment temperature and time, the peroxidase activity improved while the lipase activity decreased to a certain extent without significant changes. The total saturated and unsaturated fatty acids were significantly unchanged during storage, while oleic/linoleic acid increased substantially by 1% at 120 °C for 88 min. The increase in treatment time and temperature was beneficial in controlling the fatty acid values. However, extended treatment time caused an increase in the peroxide value and MDA. The essential and non-essential amino acid ratios, which evaluate a protein's nutritional value, remained relatively stable. The essential subunit of rice bran protein was not affected by the temperature and time of dry heat treatment and storage time.

In situ Phenotyping of Grapevine Root System Architecture by 2D or 3D Imaging: Advantages and Limits of Three Cultivation Methods.

The root system plays an essential role in the development and physiology of the plant, as well as in its response to various stresses. However, it is often insufficiently studied, mainly because it is difficult to visualize. For grapevine, a plant of major economic interest, there is a growing need to study the root system, in particular to assess its resistance to biotic and abiotic stresses, understand the decline that may affect it, and identify new ecofriendly production systems. In this context, we have evaluated and compared three distinct growing methods (hydroponics, plane, and cylindric rhizotrons) in order to describe relevant architectural root traits of grapevine cuttings (mode of grapevine propagation), and also two 2D- (hydroponics and rhizotron) and one 3D- (neutron tomography) imaging techniques for visualization and quantification of roots. We observed that hydroponics tubes are a system easy to implement but do not allow the direct quantification of root traits over time, conversely to 2D imaging in rhizotron. We demonstrated that neutron tomography is relevant to quantify the root volume. We have also produced a new automated analysis method of digital photographs, adapted for identifying adventitious roots as a feature of root architecture in rhizotrons. This method integrates image segmentation, skeletonization, detection of adventitious root skeleton, and adventitious root reconstruction. Although this study was targeted to grapevine, most of the results obtained could be extended to other plants propagated by cuttings. Image analysis methods could also be adapted to characterization of the root system from seedlings.

Model of Short- and Long-Term Outcomes of Emicizumab Prophylaxis Treatment for Persons with Hemophilia A.

BACKGROUND: Hemophilia A (HA) can result in bleeding events because of low or absent clotting factor VIII (FVIII). Prophylactic treatment for severe HA includes replacement FVIII infusions and emicizumab, a bispecific factor IXa- and factor X-directed antibody. OBJECTIVE: To develop an economic model to predict the short- and long-term clinical and economic outcomes of prophylaxis with emicizumab versus short-acting recombinant FVIII among persons with HA in the United States. METHODS: A Markov model was developed to compare clinical outcomes and costs of emicizumab versus FVIII prophylaxis among persons with severe HA from U.S. payer and societal perspectives. Patients started prophylaxis at age 1 year in the base case. Mutually exclusive health states considered were "no arthropathy," "arthropathy," "surgery," and "death." Serious adverse events, breakthrough bleeds, and inhibitor development were simulated throughout the modeled time horizon. In addition to the prophylaxis drug costs, patients could incur other direct costs related to breakthrough bleeds treatment, serious adverse events, development of inhibitors, arthropathy, and orthopedic surgery. Indirect costs associated with productivity loss (i.e., missed work or disabilities) were applied for adults. Model inputs were obtained from the HAVEN 3 trial, published literature, and expert opinion. The model used a lifetime horizon, and results for 1 year and 5 years were also reported. Deterministic sensitivity analyses and scenario analyses were conducted to assess robustness of the model. RESULTS: Over a lifetime horizon, the cumulative number of all treated bleeds and joint bleeds avoided on emicizumab versus FVIII prophylaxis were 278.2 and 151.7, respectively. Correspondingly, arthropathy (mean age at onset: 12.9 vs. 5.4 years) and FVIII inhibitor development (mean age at development: 13.9 vs. 1.1 years) were delayed. Total direct and indirect costs were lower for emicizumab versus FVIII prophylaxis for all modeled time horizons ($97,159 vs. $331,610 at 1 year; $603,146 vs. $1,459,496 at 5 years; and $15,238,072 vs. $22,820,281 over a lifetime horizon). The sensitivity analyses indicated that clinical outcomes were sensitive to efficacy inputs, while economic outcomes were driven by the discount rate, dosing schedules, and treatments after inhibitor development. Results for moderate to severe patients were consistent with findings in the severe HA population. CONCLUSIONS: The model suggests that emicizumab prophylaxis confers additional clinical benefits, resulting in a lower number of bleeding events and delayed onset of arthropathy and inhibitor development across all time assessment horizons. Compared with short-acting recombinant FVIII, emicizumab prophylaxis leads to superior patient outcomes and cost savings from U.S. payer and societal perspectives. DISCLOSURES: Funding for this study was provided by Genentech. Raimundo and Patel are employees of Genentech and own stock or stock options. Zhou, Han, Ji, Fang, Zhong, and Betts are employees of Analysis Group, which received consultancy fees from Genentech for conducting this study. Mahajerin received consultancy fees from Genentech for work on this study. Portions of this research were presented as a poster at the 2018 American Society of Hematology Conference; December 1-4, 2018; San Diego, CA.

Comparison of Characteristics of Benign Prostatic Hyperplasia (BPH) Patients Treated with Finasteride and Alpha Blocker Combination Therapy Versus Alpha Blocker Monotherapy in China: An Analysis of Electronic Medical Record Data.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is commonly treated with 5-alpha-reductase inhibitor/alpha blocker combination therapy or with alpha blocker monotherapy. However, in China, the characteristics of BPH patients receiving 5-alpha-reductase inhibitor/alpha blocker combination therapy or alpha blocker monotherapy remain largely unknown. Therefore, this study compared the characteristics of BPH patients receiving either the 5-alpha-reductase inhibitor finasteride in combination with an alpha blocker or an alpha blocker as monotherapy in clinical practice in China. METHODS: Data were obtained from a large electronic medical record database from four tertiary hospitals in major cities in China (2009-2016). BPH patients aged ≥ 50 years with ≥ 1 alpha blocker fill on/after the first BPH diagnosis were selected. Patients were further classified as receiving combination therapy (≥ 1 overlapping day of supply for finasteride and an alpha blocker) or alpha blocker monotherapy (did not receive any 5-alpha-reductase inhibitor). Patient characteristics, visit type (in- vs. outpatient) at treatment initiation, and comorbidities were evaluated during the 6-month baseline period and compared between the two groups using two sample t tests and chi-square tests/Fisher's exact tests. RESULTS: A total of 2666 and 2738 patients received combination therapy and monotherapy, respectively. The combination group was older (70.3 vs. 67.3 years, p < 0.0001) and had more patients initiated in an inpatient setting (46.0% vs. 26.4%, p < 0.0001). Compared with the monotherapy group, the combination group had more comorbidities, such as hypertension (48.3% vs. 35.6%, p < 0.0001), cardiovascular disease (65.3% vs. 48.0%, p < 0.0001), and diabetes (21.1% vs. 15.7%, p < 0.0001), and a higher Charlson comorbidity index (0.9 vs. 0.7, p < 0.0001). CONCLUSION: Chinese BPH patients using finasteride/alpha blocker combination therapy were older and had a higher comorbidity burden than those using alpha blocker monotherapy. These findings provide Chinese healthcare decision-makers with a better understanding of the patient characteristics generally associated with BPH combination therapy vs. alpha blocker monotherapy. FUNDING: Merck Sharp and Dohme (China) Co., Ltd., Shanghai, China.

Cost-effectiveness of ceritinib in previously untreated anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer in the United States.

AIMS: To assess the cost-effectiveness of first-line ceritinib vs crizotinib and platinum doublet chemotherapy for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) from a US third-party payer's perspective. MATERIALS AND METHODS: A partitioned survival model with three health states (stable disease, progressive disease, death) was developed over a 20-year time horizon. Ceritinib's efficacy inputs (progression-free and overall survival) were estimated from ASCEND-4; parametric survival models extrapolated data beyond the trial period. The relative efficacy of ceritinib vs chemotherapy was obtained from ASCEND-4, the relative efficacy of ceritinib vs crizotinib was estimated using a matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014. Drug acquisition, treatment administration, adverse event management, and medical costs were obtained from publicly available databases and the literature, and inflated to 2016 US dollars. Treatment-specific stable-state utilities were derived from trials and progressive-state utility from the literature. Incremental costs per quality-adjusted life year (QALY) were estimated for ceritinib vs each comparator. Cost-effectiveness was assessed based on US willingness-to-pay thresholds. Deterministic and probabilistic sensitivity analyses were performed to test model robustness. RESULTS: In the base case, first-line ceritinib was associated with total direct costs of $299,777 and 3.28 QALYs (from 4.61 life years gained [LYG]) over 20 years. First-line crizotinib and chemotherapy were associated with 2.73 and 2.41 QALYs, 3.92 and 3.53 LYG, and $263,172 and $228,184 total direct costs, respectively. The incremental cost per QALY gained was $66,064 for ceritinib vs crizotinib and $81,645 for ceritinib vs chemotherapy. In the first 2 years following treatment initiation, ceritinib dominated crizotinib by conferring greater health benefits at reduced total costs. Results were robust to deterministic and probabilistic sensitivity analyses. LIMITATIONS: In the absence of head-to-head trials, an indirect comparison method was used. CONCLUSIONS: Ceritinib is cost-effective compared to crizotinib and chemotherapy in the treatment of previously untreated ALK-positive metastatic NCSLC in the US.

Dynamic evolution of pulsating solitons in a dissipative system with the gain saturation effect.

We numerically investigate the dynamic evolution of pulsating solitons based on complex cubic-quintic Ginzburg-Landau equation with gain dynamics effects. We show that an additional soliton can be generated by the disturbance caused by a dispersion wave emitted by a single-period pulsating soliton and these solitons form soliton molecule. More complicated oscillating processes, such as snaking pulsation and double-periodic pulsation are actuated by periodic collision of the entangled solitons. Moreover, the dispersive wave, caused by high gain parameters and the soliton collision, appears periodically which is in sync with the pulsating process. These results are consistent with the recent experiments of soliton pulsations measured by dispersive Fourier transform techniques, and will stimulate further experimental research of the complex multi-soliton bunches in dissipative systems.

RhizoTubes as a new tool for high throughput imaging of plant root development and architecture: test, comparison with pot grown plants and validation.

BACKGROUND: In order to maintain high yields while saving water and preserving non-renewable resources and thus limiting the use of chemical fertilizer, it is crucial to select plants with more efficient root systems. This could be achieved through an optimization of both root architecture and root uptake ability and/or through the improvement of positive plant interactions with microorganisms in the rhizosphere. The development of devices suitable for high-throughput phenotyping of root structures remains a major bottleneck. RESULTS: Rhizotrons suitable for plant growth in controlled conditions and non-invasive image acquisition of plant shoot and root systems (RhizoTubes) are described. These RhizoTubes allow growing one to six plants simultaneously, having a maximum height of 1.1 m, up to 8 weeks, depending on plant species. Both shoot and root compartment can be imaged automatically and non-destructively throughout the experiment thanks to an imaging cabin (RhizoCab). RhizoCab contains robots and imaging equipment for obtaining high-resolution pictures of plant roots. Using this versatile experimental setup, we illustrate how some morphometric root traits can be determined for various species including model (Medicago truncatula), crops (Pisum sativum, Brassica napus, Vitis vinifera, Triticum aestivum) and weed (Vulpia myuros) species grown under non-limiting conditions or submitted to various abiotic and biotic constraints. The measurement of the root phenotypic traits using this system was compared to that obtained using "classic" growth conditions in pots. CONCLUSIONS: This integrated system, to include 1200 Rhizotubes, will allow high-throughput phenotyping of plant shoots and roots under various abiotic and biotic environmental conditions. Our system allows an easy visualization or extraction of roots and measurement of root traits for high-throughput or kinetic analyses. The utility of this system for studying root system architecture will greatly facilitate the identification of genetic and environmental determinants of key root traits involved in crop responses to stresses, including interactions with soil microorganisms.